The present invention relates to the commercial poultry industry and more particularly to a vaccine against Newcastle disease found in fowl.
Newcastle disease is a viral infection widely distributed throughout the world. The etiologic agent, Newcastle disease virus, is a paramyxovirus of the Family Paramyxoviridae and is classified as serotype I. In general, Newcastle disease is an acute febrile and contagious disease of fowls resembling fowl plague. It is usually characterized by high infectivity with respiratory and nervous symptoms in affected animals. Newcastle disease is transmissible to man, in whom it causes a severe, but transient conjunctivitis. The disease is of particular concern to the commercial poultry industry, in which the economic losses due to livestock morbidity and mortality can be enormous. Several forms of the disease have been identified including velogenic viscerotropic Newcastle disease, velogenic neurotropic Newcastle disease, mesogenic Newcastle disease, and lentogenic Newcastle disease (Beard, C. W. and Hanson, R. P.: Newcastle disease, in Diseases of Poultry, 8th Edition, edited by M. S. Hofstad. Iowa State University Press, Ames, Iowa, 1984).
Velogenic viscerotropic Newcastle disease is produced by highly pathogenic strains of Newcastle disease virus and is characterized by high mortality with severe lesions in the gastrointestinal tract. Although present in most other areas of the world, it is not found in the United States. The last outbreak of velogenic viscerotropic Newcastle disease occurred in California during 1970-74 and cost the United States Department of Agriculture (USDA) more than 60 million dollars to eradicate the disease.
Velogenic neurotropic Newcastle disease is also produced by highly pathogenic strains of Newcastle disease virus. This disease is characterized by severe neurological symptoms in infected animals. In most cases, the infected animals do not survive. Velogenic neurotropic Newcastle disease is very seldom seen today in the United States, although it is relatively widespread in other parts of the world.
Mesogenic Newcastle disease is caused by Newcastle disease virus strains that are intermediate in pathogenicity. It is found throughout the world in various fowl.
Lastly, lentogenic Newcastle disease is caused by mildly pathogenic strains of Newcastle disease virus and is characterized mainly by respiratory signs. This form of the disease is quite commonplace in the commercial poultry industry and results in economic losses due to livestock loss, poor livestock growth, feed conversion, and increased livestock carcass condemnation at processing.
In an effort to curtail the economic losses due to Newcastle disease in the commercially poultry industry, young chickens have been routinely vaccinated against the Newcastle disease virus. The vaccines used are prepared with live attenuated Newcastle disease virus derived from lentogenic-type strains and confer immunity against all forms of Newcastle disease.
Chickens are typically inoculated by mass administration procedures including the distribution of the live virus vaccine in drinking water and the spraying of the vaccine directly onto the chickens. In some parts of the world where labor is available and not expensive, chickens are vaccinated with live attenuated emulsified vaccines by injecting each chicken individually. The live virus, once inside the chicken, replicates in the respiratory tract and is spread horizontally from chicken to chicken by aerosol and direct contact routes. Thus, a flock immunity to the various forms of Newcastle disease is established in a relatively short amount of time.
Live virus vaccines have been found to be more desirable than "killed" or inactivated vaccines for use in the commercial poultry industry. A live virus vaccine induces active immunization in a shorter time period than does a "killed" or inactivated vaccine and generally provides both local and durable humoral immunity. The "killed" vaccines require the use of large amounts of antigen to induce immunity, whereas live vaccines are routinely administered in small doses. The "killed" vaccines are also required to be administered parenterally, which is a tedious process. Live vaccines, on the other hand, are easily mass administered by aerosol, spray or drinking water form. Further, live virus vaccines, prepared by growing viruses in cell cultures or chicken embryos, are usually devoid of any potentially allergenic substances, i.e. antibiotics, preservatives, etc., that are sometimes found in "killed" virus preparations.
The use of live virus vaccines in the commercial poultry industry, however, has not been without serious drawbacks. Active immunization with live attenuated vaccines frequently induces a subclinical or mild clinical illness which duplicates, to a limited extent, the disease that is marked for prevention. In the case of chickens inoculated with live attenuated Newcastle disease virus derived from lentogenic-type strains, the replication of the live virus in the respiratory tissues induces a respiratory reaction which is actually a mild form of Newcastle disease.
The respiratory reaction, when uncomplicated, is usually overcome by the natural immunogenic defense mechanisms of the chicken. Both the chicken and the flock will then develop the desired immunity to the Newcastle disease virus. Young chicks have the additional protection of maternal antibodies transmitted from the parent via the yolk sac, and these maternal antibodies decrease, but do not eliminate, the respiratory reaction.
A problem arises, however, when the respiratory reaction becomes complicated due to negative influences found in the chicken breeding environment. These negative influences include the accumulation of dust or ammonia, other concurrent organisms infecting the chickens, and high chicken stocking density. The respiratory reaction in these situations results in severe respiratory symptoms that produce heavy chicken losses even when costly therapy is instituted. Should the chickens not be immediately lost due to illness, the resulting poor growth, feed conversion, and increased carcass condemnation at processing can still add up to a significant economic loss.
Therefore, a need exists for a Newcastle disease virus vaccine of the live attenuated type that is capable of producing solid immunity against all forms of the disease, but that is without the side effects of respiratory or other undesirable reactions in inoculated animals.
Another problem in the present use of live attenuated lentogenic virus strains as vaccines against Newcastle disease is the tendency for the induced flock immunity to be non-uniform and of short duration. This is due primarily to the action of the maternal antibodies found in young chickens of vaccine age. The maternal antibodies tend to neutralize the vaccine virus, ability to replicate and thus prevent the vaccine virus from inducing a solid immunization response. Therefore, there exists a need for a live attenuated Newcastle disease virus vaccine capable of inducing solid immunity in the presence of maternal antibodies.
A further disadvantage of currently used live attenuated lentogenic vaccines is the complicated and costly processing necessary to attenuate the pathogenic virus marked for use as a vaccine. The artificial attenuation is typically accomplished by the passage of the virus through multiple systems (chicken embryos, chicken embryo primary cell cultures, cell lines of different origin, etc.) until an acceptable attenuated virus is obtained. A naturally attenuated lentogenic virus, on the other hand, would be beneficial in eliminating these processing steps and in providing for a more reliable attenuated strain. Therefore, there also exists a need for a live attenuated Newcastle disease virus vaccine that would not require artificial attenuation before use.
A new live attenuated virus used as a Newcastle disease vaccine should also be capable of being administered to chickens in a manner compatible with current mass inoculation procedures. These include inoculating by drinking water and direct spray. Therefore, there exists a further need for a live attenuated Newcastle disease virus vaccine capable of being administered by current mass inoculation techniques.
As a new live attenuated virus vaccine against Newcastle disease must be economically advantageous for use in the commercial poultry industry, the new virus must be capable of being produced in a manner that is cost effective. A virus vaccine that could be produced using already existing commercial virus production technology would be particularly advantageous in keeping production costs down, as much of the set-up and re-tooling costs would be eliminated. The virus vaccine should also have a yield of manufacturing similar to, or greater than, the existing live attenuated vaccine manufacturing method to be economically desirable. Therefore, there exists still a further need for a new live attenuated Newcastle disease virus vaccine capable of being produced using existing commercial virus production technology.